An important aim of ongoing research in the disposable medical device industry is to provide soft, non-tacky packaging suitable for contact with human skin without the use of plasticizers. A further aim of ongoing research is to provide flexible packaging for biological and pharmaceutical materials, which does not become brittle while undergoing liquid nitrogen storage.
Films used in the fabrication of disposable medical devices require several specific attributes. Among the attributes are clarity, ability to seal using radio frequency (RF), flexibility, conformance to United States Pharmacopoeia (USP) Class VI and European Pharmacopoeia 3rd edition 3.1.6 test protocol, extremely low levels of extractables, excellent barriers to water vapor transmission, permeability to gases, resistance to change during sterilization via autoclaving, gamma radiation, or ethylene oxide, and, as required, compatibility with medical products contained in the disposable medical device. In addition, it is desirable that the films have a soft, non-tacky texture because they will come in contact with human skin.
In certain applications, it is required that the disposable medical devices be capable of prolonged storage in liquid nitrogen. A film that remains flexible and does not become brittle when stored in liquid nitrogen is required for storage of biological products, such as stem cells and bone marrow.
In addition, the film used for packaging medical products should have extremely low levels of extractable and leachable materials to avoid contamination of the stored material. For example, anti-cancer pharmaceuticals, such as taxol, are particularly prone to contamination by plasticizers, such as oils, leaching from conventional storage bags. In another example, extractable metals, such as aluminum, are unacceptable for peritoneal dialysis uses. Aluminum levels above about 11 ppb exacerbate certain illnesses, including anemia and encephalopathy.
Polyvinyl chloride (PVC) films conform to a number of these requirements and are conventionally used as a flexible medical product packaging material. PVC provides a relatively inexpensive, clear, soft, and flexible film for medical products packaging. In addition, PVC is relatively inert and contains low levels of extractable materials. However, to impart softness and flexibility to PVC films, plasticizers are added to PVC resins. The plasticizers are typically oils added in the hundreds of ppm range. While the amount of oil is acceptable for many medical end uses, plasticizer tends to leach from the film. The amount of plasticizer that leaches from the PVC film is unacceptable for storage of certain pharmaceuticals, such as the anti-cancer drug taxol.
PVC formulations also require a heat stabilizer to prevent the PVC from undergoing heat degradation and color change during and after processing. Heat stabilizers are extracted from the PVC by aqueous solutions stored in the bag.
Another important characteristic of biological packaging is gas permeability. Living cells, such as red blood cells and platelets, need to exchange oxygen and carbon dioxide. PVC gas permeability decreases as plasticizer levels decreases. Thus as the amount of plasticizer is increased to provide high gas permeability in PVC based medical bags, the amount of plasticizer used and the amount of plasticizer that leaches into the stored material also increases.
PVC is not suitable for liquid nitrogen storage of biological materials, such as stem cells or bone marrow. PVC becomes brittle when stored in liquid nitrogen.
Various replacements for PVC film as a component of disposable medical devices have been disclosed. U.S. Pat. No. 4,140,162 discloses clear, blow-moldable medical packaging. However, the disclosed composition comprises an antioxidant material and Kraton G, a styrene-ethylene-butylene-styrene copolymer (SEBS). SEBS is tacky and rubbery and does not provide the soft PVC-like texture desired for human skin contact.
U.S. Pat. No. 4,440,815 discloses a clear, flexible, thermoplastic medical liquid container comprising a mixture of SEBS, polypropylene, ethylene-lower alkyl acrylate polymer, and mineral oil. The mineral oil is added to improve clarity and flexibility. However, mineral oil is susceptible to leaching and subsequent contamination of the material stored in the medical liquid container.
U.S. Pat. No. 4,814,375 discloses a soft, high strength elastomeric composition for use in medical and pharmaceutical products comprising SEBS, a mineral oil plasticizer to soften the SEBS, and an acrylic resin.
U.S. Pat. No. 4,479,989 discloses a film material for use in sterilized medical solution containers comprising linear low-density polyethylene (LLDPE) and SEBS.
U.S. Pat. No. 6,017,598 discloses a medical bag comprising multiple polymer film layers, wherein one of the layers comprises a matrix comprising a block copolymer, such as SEBS, and a polyolefin.
EP 0 740 544 B1 discloses a plastic formulation for a storage container for blood components comprising an ethylene-vinyl acetate copolymer (EVA), SEBS, and ultra-low density polyethylene (ULDPE).
The term “disposable medical devices” as used herein, is not to be limited to the specifically disclosed embodiments. Disposable medical devices, as used herein, includes storage containers for medical products, such as blood component bags, peritoneal dialysis sets, drainage collection bags, intravenous solution storage, and drug delivery systems.
The term “medical products” as used herein, is not to be limited to the specifically disclosed embodiments. Medical products, as used herein, includes nutritional products; biological products, such as stem cells, blood components, and bone marrow; and pharmaceutical products, such as peritoneal dialysis solutions and drugs, such as taxol.
The term “essentially free of leachable material”, as used herein, means there is either no leachable material in the flexible monolayer elastomer film or the amount of leachable material is so low as to not adversely affect the medical products stored within disposable medical devices formed from the flexible monolayer elastomer film. No leachable materials, such as plasticizers, are added to the elastomer film material. The flexible monolayer elastomer films meet the European Pharmacopoeia 3rd edition 3.1.6 and USP Class VI test protocols.
The term “texture”, as used herein, means the tactile quality of the surface of the flexible monolayer elastomer film.
The term “the texture being substantially that of plasticized polyvinyl chloride”, as used herein, means that the texture of the flexible monolayer elastomer film is like that of plasticized polyvinyl chloride films conventionally used in disposable medical devices, such as the films in Comparative Examples 1-5 of the instant disclosure.